ORIGINAL ARTICLE
ECHOCARDIOGRAPHIC EVALUATION OF DIASTOLIC DYSFUNCTION IN
ASYMPTOMATIC TYPE 2 DIABETES MELLITUS PATIENTS
Madhumathi R1, Prakash Kikkeri Gowdaiah2, Amogh Dudhwewala3, Chaithra A. N4, Tejaswini Dande5
HOW TO CITE THIS ARTICLE:
Madhumathi R, Prakash Kikkeri Gowdaiah, Amogh Dudhwewala, Chaithra A. N, Tejaswini Dande,
“Echocardiographic Evaluation of Diastolic Dysfunction in Asymptomatic Type 2 Diabetes Mellitus patients”.
Journal of Evolution of Medical and Dental Sciences 2014; Vol. 3, Issue 01, January 06; Page: 200-209.
ABSTRACT: INTRODUCTION:As per the latest edition of International Diabetes Federation(IDF)
Diabetes Atlas, diabetes mellitus currently affects approximately 371 million people worldwide, and
majority (90%-95%) have type 2 diabetes mellitus, which is considered a metabolic cum vascular
disease. The morbidity and mortality due to type 2 DM is due to its micro and macrovascular
complications which affect nearly every organ system in the body – particularly heart. There is a
marked increase in incidence of congestive heart failure, coronary artery disease in diabetic patients.
The relative risk of developing heart failure is 3.8 in diabetic men and 5.5 in diabetic women, when
compared with non-diabetic individuals. Despite similar left ventricular systolic dysfunction,
patients with diabetes have more pronounced heart failure symptoms, use more diuretics, and have
an adverse prognosis compared with those without diabetes; one putative explanation for these
discrepancies is diastolic dysfunction of the left ventricle in diabetes mellitus. Left ventricular
diastolic dysfunction thus represent the first stage of diabetic cardiomyopathy preceding changes in
systolic function. The diastolic abnormalities are present in diabetic patients without overt diabetic
complications of cardiovascular system, reinforcing the importance of early examination of
ventricular function in individuals with diabetes mellitus. MATERIALS AND METHODS: This was a
cross sectional study, conducted over a period of one year from August 2012 to August 2013. 50
patients with type 2 DM who had no symptoms of cardiovascular disease with normal BP and
normal ECG were enrolled. Informed consent was obtained from the patients and they underwent a
thorough physical examination, supported by laboratory investigations. A Doppler 2D echo was
done in each patient and a calculation of LV ejection fraction, LA dimension, E velocity, A velocity
and E/A ratio were done. E/A ratio of < 1with increased LA size and normal ejection fraction of >
60% was used as echo diagnostic criteria for LV diastolic dysfunction. RESULTS: Our study consisted
of 50 patients with type 2 DM, 30(60%) were females and 20(40%) males. Majority of patients were
in the age group of 40 – 70 years. Diastolic dysfunction was present in 24(48%) patients out of
whom 8 were males and 16 females. The maximum number of patients with LV diastolic dysfunction
was in age group 50 – 59 years. There was a linear increase in prevalence of diastolic dysfunction
with increasing age, increased duration of diabetes mellitus and increasing HbA1c levels. There was
also significant correlation between LV diastolic dysfunction (LVDD) and microangiopathy. Out of 13
patients who had diabetic retinopathy, 8 patients had LVDD and out of 11 patients with
microalbuminuria, 9 patients had LVDD.CONCLUSION: LV diastolic dysfunction is an early
manifestation of diabetic cardiomyopathy. Its prevalence correlates with duration of diabetes,
HbA1c values and presence of microangiopathy. LVDD contributes significantly to morbidity of
congestive heart failure in diabetic patients. Echocardiography is a very useful noninvasive tool in
detecting LVDD in asymptomatic type 2 DM patients.
KEY WORDS: Type 2 diabetes mellitus, LV diastolic dysfunction, Echocardiography.
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ORIGINAL ARTICLE
INTRODUCTION: Diabetes mellitus is a chronic illness that requires continuing medical care and
ongoing patient self-management education and support to prevent acute complications and to
reduce the risk of long-term complications. Diabetes care is complex and requires multifactorial risk
reduction strategies beyond glycemic control. Its incidence is increasing rapidly, and by 2030, this
number is estimated to almost double1. The greatest increase in prevalence is, however, expected to
occur in Asia and Africa.2
India has more diabetics than any other country in the world, according to the International
Diabetes Foundation. The disease affects more than 50 million Indians - 7.1% of the nation's adults and kills about 1 million Indians a year. The average age on onset is 42.5 years.3
Diabetes and Heart: The existence of a diabetic cardiomyopathy was first proposed by Rubler et
al4in 1972 on the basis of postmortem findings.In 1974, Framingham study showed that heart failure
was more common in diabetes due to diabetic cardiomyopathy. The Framingham Study, which
involved 5209 patients followed up for 18 years, demonstrated that patients with diabetes had a
greater likelihood of developing clinical heart failure. The relative risk of developing heart failure
was 3.8 in diabetic men and 5.5 in diabetic women compared with nondiabetic patients. The study
also revealed a marked increase in congestive heart failure, coronary artery disease and myocardial
Infarction in diabetic patients.4
Patients with signs and symptoms of heart failure with preserved left ventricular systolic
function i.e., ejection fraction of 60 % are said to have diastolic heart failure (DHF). Diabetes mellitus
is one of the major risk factors for DHF. The mortality rates among the patients with diastolic heart
failure ranges from 5-8 % annually as compared with 10-15% among patients with systolic heart
failure. In Framingham heart study, it was shown that patients with diabetes mellitus carry an
increased risk for coronary heart disease. Framingham data suggests that hyperglycemia as such is
an independent risk factor.4, 5
The leading cause of LV systolic dysfunction and congestive heart failure in developed
countries is coronary heart disease (CHD), with a prevalence in the recent multicenter heart failure
trials of 66%. Thus, ischemic heart disease often contributes to the manifestation of heart failure,
and the progression of heart failure in many cases may be a reflection of progression of CHD. This
indicates that the prevention and treatment of heart failure in many patients should include use of
established primary and secondary prevention guidelines, including control of blood pressure, use of
statins and aspirin, smoking cessation, and implementation of ACEI therapy in persons with diabetes
and cardiovascular riskfactors.6
Despite similar left ventricular systolic dysfunction, patients with diabetes have more
pronounced heart failure symptoms, use more diuretics, and have an adverse prognosis compared
with those without diabetes; one putative explanation for these discrepancies is diastolic
dysfunction of the left ventricle in diabetes mellitus.7 Left ventricular diastolic dysfunction thus
represent the first stage of diabetic cardiomyopathy preceding changes in systolic function,
reinforcing the importance of early examination of ventricular function in individuals with
diabetes.8, 9
The diastolic abnormalities are present in diabetic patients without overt diabetic
complications of cardiovascular system, 10 itis the earliest and specific functional abnormality in
diabetic cardiomyopathy and can affect patients who are free of macrovascular complications, even
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ORIGINAL ARTICLE
in newly diagnosed diabetes mellitus patients or in those with a disease duration of less than 1
year.11
Diastole encompasses the time period during which the myocardium loses its ability to
generate force and shorten and returns to an unstressed length and force 12. By extension, diastolic
dysfunction occurs when these processes are prolonged, slowed, or incomplete. Moreover, if
diastolic function is truly normal, it must remain normal both at rest and during the stress of a
variable heart rate, stroke volume, end-diastolic volume, and blood pressure.
Diastolic dysfunction refers to a condition in which abnormalities in mechanical function are
present during diastole. The causes of diastolic dysfunction may be subdivided into a decrease in
passive myocardial diastolic compliance, and an impairment in active LV relaxation. Abnormalities
in diastolic function may occur in the presence or absence of a clinical syndrome of heart failure and
with normal or abnormal systolic function. Therefore, whereas diastolic dysfunction describes an
abnormal mechanical property, diastolic heart failure describes a clinical syndrome8.
MATERIALS AND METHODS: This was a cross sectional study conducted at Victoria Hospital and
Bowring and Lady Curzon Hospital, both of which are affiliated to Bangalore Medical College and
Research Institute, Bangalore, over a period of one year between August 2012 to August 2013.
Inclusion criteria: The study comprised of a total of 50 cases type 2 diabetes mellitus, which
clinically had no symptoms of cardiovascular disease and normal blood pressure of < 130/80 mmHg,
with normal ECG.
Exclusion criteria: All patients with type 2 diabetes mellitus with overt cardiac diseases like
Ischemic and hypertensive heart disease congestive heart failure, valvular heart disease, and
cardiomyopathy were excluded from the study.
Informed consent was obtained from the subjects. Patients underwent thorough clinical
examination supported by relevant investigations.
The patients underwent the following investigations.
a. ECG.
b. FBS, PPBS.
c. Urea, creatinine.
d. Glycosylated haemoglobin (HbA1c).
e. Urine albumin.
f. Fasting Lipid profile.
g. Fundus examination.
h. Echocardiography.
i. Doppler Echo was done in each patient and 3-4 cardiac cycles were analysed to get best
phase for better outcome of results. Ejection fraction was calculated in all patients.
In Doppler study following values were evaluated.
a. E-peak velocity of early mitral flow
b. A- peak velocity of late mitral flow
c. E/A ratio
d. Left atrial size
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ORIGINAL ARTICLE
Reduction in E velocity increase over A velocity with E/A ratio of <1 and increase in left
atrial (LA) size were considered as the evidence of left ventricular diastolic dysfunction (DD).
Statistical analysis was done by estimating the prevalencerate of diastolic dysfunction and
co-relating with the with glycemic control.
RESULTS: Our study consisted of 50 patients with type 2 DM, among whom 30(60%) were females
and 20 (40%) males. Most of the subjects were in 40-70 years age group(Table 1, Table2).
Diastolic Dysfunction
Percentage
Present
Absent
Present Absent
Males
20
8
12
40%
60%
Females
30
16
14
53%
47%
Table 1:Correlation between gender and diastolic dysfunction
Gender
Total
Diastolic dysfunction was present in 24 (48%) of the cases amongthem, 8 were males, 16
were females. Though statistically not significant, diastolic dysfunction was more prevalent in
females.
Out of 24(48%) with Diastolic dysfunction maximum prevalence was found in 50-59years
age group. 8(57.14%) patients out of 14 in this group had diastolic dysfunction. In patients in the age
group 60-69years 6(50%) patients of 12 had diastolic dysfunction. Among the age group of 50 –
59years and 60 – 69years, diastolic dysfunction was almost comparable. There was a linear increase
in the prevalence of diastolic dysfunction with the increasing age.
No of cases
Diastolic dysfunction
Percentage
Male Female Total
Present
Absent
30-39
2
5
7
14
1
6
40-49
5
7
12
24
4
8
50-59
4
10
14
28
8
6
60-69
7
5
12
24
6
6
70-above
2
3
5
10
5
0
Total
20
30
50
100
24
26
Table 2: Age wise distribution and correlation with diastolic dysfunction
Age wise distribution
Comparing with duration of diabetes, we had 21(42%) patients with less than 5 year
duration of diabetes and 20(40%) patients with 5-10 years duration of diabetes. Statistically it was
significant as we had higher percentage of patients with diastolic dysfunction as duration of diabetes
increased(table 3, Fig 1).
Duration in year
0-5
6-10
11-15
>15
Total
No of cases
Diastolic dysfunction
Percentage
Male Female Total
Present
Absent
6
15
21
42
7
14
10
10
20
40
10
10
3
4
7
14
5
2
1
1
2
2
2
0
20
30
50
100
24
26
Table 3: Duration of diabetes and correlation with diastolic dysfunction
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ORIGINAL ARTICLE
Fig. 1: Correlation between duration of diabetes diastolic dysfunction
Patients receiving OHAS were more 32 (64%) compared to 11 (22%) patients who were on
insulin. And 7(14%) patients were on both insulin and OHAs(Table 4).
Type of Treatment
Total
OHA
Insulin
Both
Total
32
11
7
50
Diastolic Dysfunction
Present
Absent
14
18
6
5
4
3
24
26
Table 4: Correlation between type of treatment and diastolic dysfunction
25(50%) subjects had HbA1c >8 %which indicated poor glycemic control (Table 5).
Prevalence of diastolic dysfunction increased gradually with the rise in HbA1c levels and it was
statistically significant as shown in (Table 5 Fig 2). Diastolic dysfunction was present in 6 patients
out of 24with HbA1c between <8%. 18(75%)patients of 24 who had diastolic dysfunction had
HbA1c >8. In patients with HbA1c >10 % out of 7 patients 6 had diastolic dysfunction.
Diastolic Dysfunction
Present
Absent
6.4-7
4
1
3
7.1-8
21
5
16
8.1-10
18
12
6
>10
7
6
1
Total
50
24
26
Table 5: Correlation between HbA1C level and Diastolic Dysfunction
HbA1C level
Total
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ORIGINAL ARTICLE
Fig. 2:Correlation between HbA1C level and Diastolic Dysfunction
There were significant changes in E, A and E/A ratio in patients who had diastolic
dysfunction. Left atrial size was higher in patients who had diastolic dysfunction. The mean LA size
was 2.711 ± 0.14 in patients who did not have diastolic dysfunction and it was 3.40 ± 0.25 in patients
who had diastolic dysfunction.
There was a significant correlation with diastolic dysfunction and microangiopathy. Out of
13 patients who had diabetic retinopathy, 8 patients had diastolic dysfunction. Out of 11 patients
who had microalbuminuria, 9 had diastolic dysfunction (table 6 and 7).
Diabetic retinopathy
Diastolic Dysfunction
Present
Absent
Total
Present
8
16
24
Absent
5
21
26
Total
13
37
50
Table 6:Correlation between diabetic retinopathy and Diastolic Dysfunction
Microalbuminuria
Diastolic Dysfunction
Present
Absent
Total
Present
9
15
24
Absent
2
24
26
Total
11
39
50
Table 7:Correlation between microalbuminuria and Diastolic Dysfunction
DISCUSSION: Numerous studies have shown that impairment of the LV diastolic function may be
detected in patients with diabetes. Diastolic LV abnormalities have been initially disclosed by cardiac
catheterization. Regan et al 13demonstrated in normotensive, diabetic patients without coronary
artery disease and without clinical evidence of heart failure, increased left-ventricular end-diastolic
pressure, a decreased left-ventricular end-diastolic volume with a normal ejection fraction. Paul
Poirier et al 14 in 2001 evaluated 40 diabetic patients without clinical evidence of cardiac disease by
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ORIGINAL ARTICLE
Doppler Echocardiography and came to conclusion that diastolic function in diabetic patients was
impaired even in patients with normal systolic function.
Numerous studies in humans have explored the association of diabetes with
histopathological abnormalities of myocardium. Alterations in intramyocardial coronary arteries,
similar to those seen in other organs of diabetic patients have been reported. Endothelial
proliferation and subendothelial hyaline thickening with PAS-positive material in the vessel wall
have been described in some but not all patients with or without overt congestive heart failure 15
Capillary basement membrane thickening and capillary microaneurysms have also been observed in
hearts of diabetics 16, 17. Zoneraich et al18 who conducted their study in young normotensive type 1
diabetics, found small vessel disease in 72% of diabetic patients, while it was present in only 12% of
non-diabetic subjects.
Interstitial accumulations of advanced-glycated end products (AGEs), which include collagen,
elast in and other connective tissue proteins, as well as fibrosis in the myocardium, have been
reported in biopsy or post-mortem studies of human diabetic hearts 13, 19.The mechanism of collagen
accumulation in the diabetic myocardium seems to be due to impaired degradation rather than
enhanced synthesis20. The interstitial abnormalities could explain an increase in end-diastolic
stiffness as well as LV mass and contribute to the diastolic dysfunction13. In the less advanced forms
of tissue abnormality, the interstitial changes seem to predominate for some time and are associated
with preserved cell morphology that is consistent with normal systolic function. As a potential
diagnostic tool, it has been suggested that collagen accumulation in the extracellular matrix of the
heart is responsible for abnormal acoustic properties of the myocardium in diabetic patients.
In our study most of the patients had duration of diabetes less than 10 years. This was
because, as the duration of diabetes increased, other associated co-morbid diseases like
hypertension, IHD, would also appear and hence could not be included in our study. So the patients
with duration of diabetes more than 15 years and above age of 70 years were less. When the
treatment profile was evaluated most of the patients were on OHAS / OHAS with insulin, most of the
subjects had poor glycemic control, reasons are multifactorial Viz., poor compliance of the patient
with reference to treatment, lifestyle modifications, inadequate doses, poor regular checkup.
Left ventricular diastolic dysfunction (LVDD) was found in 24(48%) of our patients. This
prevalence of diastolic dysfunction was almost comparable with other studies as shown in (Table 8).
Studies
Paul Poirier et
Faden G et al21
al14
Markuszewski et al22
Percentage
60
64
43
Patil C et al23
54.33
Present study
48
Table 8:Comparison of diastolic dysfunction with other studies
Genderwise comparison of LVDD showed 53 % female subjects had diastolic dysfunction
compared to 40 % of males. This could be due to hormonal changes that accompany after
menopause. The prevalence of diastolic dysfunction increased with duration of diabetes. The
previous studies also confirmed the above findings.
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ORIGINAL ARTICLE
Celentano et al 25studied 64 subjects with normal glucose tolerance (n = 25), with impaired
glucose tolerance (n =15) and with type 2 diabetes mellitus (n = 24) diagnosed by an oral glucose
tolerance test according to the recommendations of the World Health Organization. They found early
signs of diastolic dysfunction (assessed by E/A mitral flow ratio), not only in patients with diabetes
but also in those with impaired glucose tolerance, independent of the confounding role of ischemia,
body weight, and blood pressure.
CONCLUSION: The prevalence of left ventricular diastolic dysfunction in asymptomatic,
normotensive patients with type 2 DM without significant coronary artery disease is much higher
than previously suspected as evidenced by the results of this study and also of similar other studies.
LV diastolic dysfunction correlated with duration of diabetes, HbA1c levels and microangiopathies,
and it contributes significantly to the morbidity of congestive heart failure in diabetic patients.
Echocardiography with measurements of diastolic functional parameters appears to be a sensitive
noninvasive method for evaluating the manifestation and course of early diabetic cardiomyopathy.
Early diagnosis and institution of treatment for LVDD in diabetic patients will reduce the morbidity
and improve the outcomes by preventing future development of heart failure.
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13. Regan TJ, Lyons MM, Ahmed SS, et al. Evidence for cardiomyopathy in familial diabetes
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systolic function. J Cardiovasc Dis Res. 2011 Oct-Dec; 2(4): 213–222
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4.
AUTHORS:
1. Madhumathi R.
2. Prakash Kikkeri Gowdaiah
3. Amogh Dudhwewala
4. Chaithra A. N.
5. Tejaswini Dande
PARTICULARS OF CONTRIBUTORS:
1. Associate Professor, Department of
Bangalore Medical College and
Institute, Bangalore.
2. Associate Professor, Department of
Bangalore Medical College and
Institute, Bangalore.
3. Post Graduate, Department of
Bangalore Medical College and
Institute, Bangalore.
5.
Medicine,
Research
Medicine,
Research
Medicine,
Research
Post Graduate, Department of
Bangalore Medical College and
Institute, Bangalore.
Post Graduate, Department of
Bangalore Medical College and
Institute, Bangalore.
Medicine,
Research
Medicine,
Research
NAME ADDRESS EMAIL ID OF THE
CORRESPONDING AUTHOR:
Dr. Prakash Kikkeri Gowdaiah,
Associate Professor,
Department of Medicine,
Bangalore Medical College and Research Institute,
Bangalore.
Email- kikkeri47@yahoo.com
Date of Submission: 20/12/2013.
Date of Peer Review: 21/12/2013.
Date of Acceptance: 27/12/2013.
Date of Publishing: 03/01/2014
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